(…) The investigators looked at two types of brain cells: adult neural stem cells, responsible for maintaining supplies of neurons and their supporting cells, and forebrain neurons, vital for performing complex cognitive tasks.
In The EMBO Journal, they reported that NAD (Nicotinamide adenine dinucleotide) levels decreased with age in the mouse hippocampus, a vital region of the brain for cognition. The researchers then used genetic techniques to find out what would happen when NAD manufacturing is turned off in the adult neural stem cells of the mouse brain.
“Neural stem cells are very metabolically expensive, so you might expect them to be particularly vulnerable to loss of an energy source,” said first author Liana Roberts Stein, PhD, postdoctoral researcher in Imai’s lab. “There are other energy sources for brain cells, such as glucose, but no one had ever looked at where NAD is coming from in these cells” (…)
The pathway begins with the B vitamin nicotinamide. Cells take dietary nicotinamide and, with a helper protein called Nampt (Nicotinamide phosphoribosyltransferase), manufacture a molecule called NMN, which then is processed further to make NAD. When Stein eliminated Nampt from neural stem cells, several significant changes took place.
Levels of NAD dropped, and the neural stem cells stopped dividing; they stopped renewing themselves; and they stopped being able to create important cells that insulate axons, the “wires” that carry electrical signals throughout the brain. With less insulation, these signals slow down, impairing brain function (…)
Imai and Stein also found they could prevent the loss of the neural stem cells missing Nampt by giving the mice NMN, the next molecule in the chain of events leading to NAD.
“We gave the mice NMN in their drinking water for 12 months,” Stein said. “And at the higher dose, we saw a rescue of the neural stem cell pool in aged mice.”
Imai called this finding exciting because it supports the possibility of a future NMN supplement.
“We think that NMN could convey a similar effect in people,” Imai said. “A future clinical trial for NMN will tell us if it has any efficacy in humans.”
In addition to maintaining stem cell populations and keeping the brain supplied with all its cell types, the investigators showed that NAD also is vital for the process of cognition itself.
Reporting in The Journal of Neuroscience, they showed that neurons of the mouse forebrain depend heavily on NAD in normal cognitive function. Instead of deleting Nampt in stem cells, this time Stein deleted it only in neurons of the forebrain. All other cells were normal, including those that make axon insulation (…)